Class II HLA antigens comprise the gene products of the HLA-DR, DQ and DP loci. These antigens have a restricted tissue distribution and mediate cell-cell interactions required to generate immune responses. Studies with a limited number of patients have shown that the level of expression of Class II HLA antigens in metastases from patients with melanoma is associated with the clinical course of the disease. After having confirmed this association on a large number of patients and with long periods of follow-up, this study will analyze immunological events as mechanisms underlying the role of Class II HLA antigens in the clinical course of melanoma. Specifically utilizing serological and immunochemical assays we will characterize primary and metastatic lesions for their expression of HLA-DR, DQ and DP antigens and we will analyze their effect on the degree of inflammatory response and on the phenotype of infiltrating cells. Furthermore we will characterize the role of HLA-DR, DQ and DP antigens i) in the proliferation of T cells stimulated with autologous melanoma cells isolated fromprimary and metastatic lesions and ii) in the immunogenicity of melanoma associated antigens recognized by monoclonal antibodies. The results of these studies in conjunction with information about the clinical course of the disease will assess the role of Class II HLA antigens in the biology of melanoma cells and the clinical significance of the detection of Class II HLA antigens on melanoma cells.